Seventh Edition Forfar & Arneil’s TEXTBOOK of PEDIATRICS Book Donated by, http:\\vip.persianss.ir Released by: tahir99 - UnitedVRG Donate to keep us alive..... 00000000773322999933..IINNDDDD ii 33//2222//22000088 55::2233::2277 AAMM Seventh Edition Forfar & Arneil’s TEXTBOOK of PEDIATRICS Edited by Neil McIntosh DSc(Med) FRCP(Edin) FRCP(Lond) FRCPCH Professor of Child Life and Health, University of Edinburgh; Honorary Consultant Paediatrician, Lothian University Hospitals NHS Trust, Edinburgh, UK Peter J. Helms MB BS PhD FRCP(Edin) FRCPCH Professor of Child Health, University of Aberdeen, Aberdeen, UK Rosalind L. Smyth MA MB BS MD FRCPCH F Med Sci Brough Professor of Paediatric Medicine, University of Liverpool, Liverpool, UK Stuart Logan MB ChB MSc(Epidemiology) MSc(politics) MRCP FRCPCH Professor of Paediatric Epidemiology; Director, Institute of Health Research, Peninsula Medical Service School, St Luke’s Campus, Exeter, UK Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2008 00000000773322999966..IINNDDDD iiiiii 33//2222//22000088 55::3377::1122 AAMM An imprint of Elsevier Limited © 2008, Elsevier Limited. All rights reserved. © 2003, Elsevier Limited. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publishers. Permissions may be sought directly from Elsevier’s Rights Department: Phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333; e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/permissions. First edition 1973 Second edition 1978 Third edition 1984 Fourth edition 1992 Fifth edition 1998 Sixth edition 2003 Seventh edition 2008 ISBN 978–0–443–10396–4 IE ISBN 978–0–443–10397–1 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging in Publication Data A catalog record for this book is available from the Library of Congress Note Knowledge and best practice in this field are constantly changing. As new research and experience broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or appropriate. Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of the practitioner, relying on their own experience and knowledge of the patient, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the Authors assumes any liability for any injury and/or damage to persons or property arising out or related to any use of the material contained in this book. The Publisher The publisher's policy is to use paper manufactured from sustainable forests Printed in China 00000000773322999922..IINNDDDD iivv 33//2222//22000088 55::2211::4400 AAMM 10001 Preface One of the most important developments in the 21st century publishing and consequently another important new feature for has been the acknowledgment that clinical practice should be this edition is a website of the text in which references listed embedded where possible in a sound evidence base. The editors in PUBMED can be accessed via the internet. We would like of this new edition of Forfar & Arneil’s Textbook of Pediatrics to acknowledge the outstanding contributions of the many continue to set contributors the challenging task of ensuring individual authors and our chapter editors, without whom this that the statements and recommendations made are based on ambitious project would not have been possible. It has been a the most robust clinical research available. The objective assess- great privilege to work with them. We would also like to thank ment of evidence and the formulation of secure recommenda- our own secretaries for their unstinting help (Elaine Forbes, tions from the evidence are gathering pace. In Child Health the Flora Buthlay, Collette Lorne and Stella Taylor) and of course evidence base, with the possible exception of disciplines such as our respective families for sharing the burden with us. oncology and neonatology, is not as comprehensive or as well defined as we would wish. This edition of Forfar & Arneil con- As with previous editions the book is produced by the Elsevier tinues to flag up the most important evidence sources for the Organization. There have been many highly professional people content of each chapter. The whole book has been revised and involved. We hope that this new 7th edition with its expanded updated and the chapter authors and editors again incorporate formal evidence base will be well received by you, the reader, where possible secure evidence of therapy, diagnosis, etiology and become as trusted a friend and guide as have previous and prognosis. This evidence is incorporated into the individ- editions. ual chapters and in the chapter reference list is starred for easy reference. We believe that the result is the most comprehensive Neil McIntosh evidence-based general textbook of pediatrics available. Our Peter J. Helms ability to access best evidence has been greatly enhanced by Rosalind L. Smyth the rapid advances of information technology and electronic Stuart Logan  10001 Contributors Ishaq Abu-Arafeh, MBBS, MD, MRCP, FRCPCH Paul L.P. Brand, MD Andrew Gavin Cleary, MB ChB BSc MSc MRCPCH Consultant in Paediatrics and Paediatric Consultant Paediatrician and Director of Consultant Paediatric Rheumatologist, Royal Neurology, Stirling Royal Infirmary, Stirling; Postgraduate Education, Princess Amalia Liverpool Children’s Hospital, Liverpool, UK Honorary Consultant Paediatrician, Fraser of Children’s Clinic, Isala klinieken, Zwolle, Allander Neurosciences Unit, Royal Hospital The Netherlands J. Brian S. Coulter, MD FRCP(I) FRCPCH Honorary Clinical Lecturer in Tropical for Sick Children, Glasgow, UK Colin E. Bruce, MB ChB FRCS FRCS(ORTH) Child Health, Liverpool School of Tropical N. Archer, MA FRCP FRCPCH DCH Consultant Paediatric Orthopaedic Medicine, Liverpool, UK Consultant Paediatric Cardiologist, Oxford Surgeon, Alder Hey Children’s Hospital, Children’s Hospital, Oxford; Honorary Liverpool, UK Jonathan Coutts, MB ChB FRCPCH FRCP(Glas) Consultant Neonatal and Respiratory Clinical Senior Lecturer, University of Oxford, Oxford, UK Helen Budge, BA BM BCh PhD MRCP FRPCH Paediatrician, The Queen Mother’s Hospital Associate Professor of Neonatology, and Royal Hospital for Sick Children, Peter D. Arkwright, FRCPCH DPhil University of Nottingham, Nottingham, Glasgow, UK Lecturer in Child Health, Department of UK Child Health, University of Manchester, Richard Coward, MB ChB MRCPCH PhD Manchester, UK Neil R.M. Buist, MB ChB FRCPE DCH MRC Clinician Scientist and Consultant Professor Emeritus, Departments of Paediatric Nephrologist, Bristol Royal Ian A. Auchterlonie, MB ChB FRCPCH FRCP Paediatrics and Medical Genetics, Oregon Hospital for Children, Bristol, UK Honorary Consultant Paediatrician (Retired), Health and Science University, Portland, Royal Aberdeen Children’s Hospital, Oregon, USA Finella Craig, BSc MBBS MRCP Consultant in Paediatric Palliative Care, Aberdeen, UK Nigel Peter Burrows, MD FRCP Great Ormond Street Hospital for Children, Alastair J. Baker, MB ChB FRCP FRCPCH Consultant Dermatologist and Associate London, UK Consultant Paediatric Hepatologist, King’s Lecturer, Department of Dermatology, College Hospital, London, UK Addenbrooke’s Hospital, Cambridge, UK Timothy J. David, MB ChB MD PhD FRCP FRCPCH DCH Susan V. Beath, BSc MB BS MRCP DTM&H FRCPCH Andrew Bush, MD FRCP FRCPCH Professor of Child Health and Paediatrics, Consultant Paediatric Hepatologist, The Professor of Paediatric Respirology, Imperial Honorary Consultant Paediatrician, The Liver Unit, Birmingham Childrens Hospital, College, London; Honorary Consultant University of Manchester, Manchester, UK Birmingham, UK Paediatric Chest Physician, Royal Brompton Hospital, London, UK Joyce E. Davidson, BSc MBChB MRCP (UK) FRCPCH Thomas F. Beattie, MB MSc FRCSEd(A&E), FCEM, Consultant Paediatric Rheumatologist, Royal FRCPE, FFSEM, DCH Gary Butler, MB BS MD FRCPCH Hospital for Sick Children, Glasgow, and Consultant in Emergency Medicine, Royal Professor of Paediatrics, Institute of Health Royal Hospital for Sick Children, Hospital for Sick Children, Edinburgh; Sciences, University of Reading and Edinburgh, UK Honorary Senior Lecturer in Paediatrics, Department of Paediatrics, Royal Berkshire University of Edinburgh, Edinburgh, UK Hospital, Reading, UK E. Graham Davies, MB BChir MA FRCPCH Consultant Paediatric Immunologist, Great Julie-Clare Becher, MB ChB MRCPCH MD Catherine M. Cale, MB ChB PhD MRCP MRCPCH Ormond Street Hospital, London, UK Consultant Neonatologist, Simpson Centre MRCPath for Reproductive Health, Royal Infirmary of Consultant in Paediatric Immunology Jan Dudley, BM MRCP(UK) FRCPCH PhD Consultant Paediatric Nephrologist, Bristol Edinburgh, Edinburgh, UK and Immunopathology, Department of Royal Hospital for Children, Bristol, UK Immunology, Great Ormond Street Hospital, W. Michael Bisset, BSc MB ChB DCH MSc MD London, UK P. Barton Duell, MD FRCPE FRCPCH Associate Professor of Medicine, Division Consultant Paediatric Gastroenterologist, Harry Campbell, MD FRCPE FFPH FRSE of Endocrinology, Diabetes, and Clinical Department of Medical Paediatrics, Royal Professor of Genetic Epidemiology and Nutrition; director, Lipid-Atherosclerosis Aberdeen Children’s Hospital, Aberdeen, UK Public Health Sciences, College of Medicine Laboratory and Metabolic Disorders Clinic, and Vet Medicine, University of Edinburgh, Peter S. Blair, PhD Edinburgh, UK Oregon Health and Science University, Medical Statistician, Senior Research Fellow, Portland, Oregon University of Bristol, Division of Child Health, Andrew J. Cant, BSc MD FRCP FRCPH Royal Hospital for Children, Bristol, UK Consultant in Paediatric Immunology and Heather Elphick, MB ChB MRCP MRCPCH MD Specialist Registrar in Respiratory Infectious Diseases, Newcastle General Paula H.B. Bolton-Maggs, FRCPCH FRCP FRCPath Hospital, Newcastle upon Tyne, UK Paediatrics, Sheffield Children’s Hospital, Consultant Haematologist, Manchester Sheffield, UK Comprehensive Care Haemophilia Centre, Michael Clarke, BSc MRCP DCH FRCPCH Department of Clinical Haematology, Consultant Paediatric Neurologist, Leeds Nicholas D. Embleton, BSc MD FRCPCH Consultant in Neonatal Medicine and Manchester Royal Infirmary, Manchester, UK Teaching Hospitals NHS Trust, Leeds, UK xv xvi Contributors Honorary Lecturer in Child Health, Newcastle Cellular Medicine, University of Newcastle and Science University, Portland, Neonatal Service, Royal Victoria Infirmary, upon Tyne, and Children’s Bone Marrow Oregon, USA Newcastle upon Tyne, UK Transplant Unit, Newcastle General Hospital, Newcastle upon Tyne, UK C. Anthony Hart, BScMB BS PhD FRCPCH FRCPath Gregory M. Enns, MB ChB Professor, Division of Medical Microbiology, Associate Professor of Pediatrics, Director, Diana Gibb, MD FRCPCH MSc School of Infection and Host Defence, Biochemical Genetics Program, Division Professor of Paediatric Epidemiology, University of Liverpool, Liverpool , UK of Medical Genetics, Stanford University, MRC Clinical Trials Unit, University College Stanford, California, USA London, London, UK Paul T. Heath, MB BS FRACP FRCPCH Senior Lecturer and Honorary Consultant, Jeremy Farrar, FRCP DPhil OBE K. Michael Gibson, PhD, FACMG Paediatric Infectious Diseases, Division Professor of Tropical Medicine Oxford Professor, Pediatrics, Pathology and Human of Child Health, St George’s University of University; Honorary Professor of Genetics, Division of Medical Genetics, London, London, UK International Health, London School of Children’s Hospital of Pittsburgh, University Hygiene and Tropical Medicine, London; of Pittsburgh School of Medicine, Pittsburgh, Peter J. Helms, MB BS PhD FRCP(Edin) FRCPCH Professor of Child Health, University of Director, Oxford University Clinical Research PA, USA Aberdeen, Aberdeen, UK Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam Barbara Golden, BSc MB BCh BAO MD FRCPI John Henderson, MD FRCP FRCPCH FRCPEd FRCPCH DCH RNutr Reader in Paediatric Respiratory Medicine, Colin D. Ferrie, BSc MB ChB MD MRCP FRCPCH Associate Dean (Medicine), Clinical Senior University of Bristol and Bristol Royal Consultant Paediatric Neurologist, Lecturer, Honorary Consultant International Hospital for Children, Bristol, UK Department of Paediatric Neurology, Leeds Child Health, Child Health Institute, General Infirmary, Leeds, UK School of Medicine, University of Aberdeen, Tom Hilliard, MD FRCPCH Royal Aberdeen Children’s Hospital, Consultant Respiratory Paediatrician, Bristol Alistair R. Fielder, FRCP FRCS FRCOphth Aberdeen, UK Children’s Hospital, Bristol, UK Professor of Ophthalmology, Department of Optometry and Visual Science, City John M. Goldsmid, BSc MSc PhD FRCPath FACTM Peter Hoare, DM FRCPsych University, London, UK FASM CBiol FIBiol FAIBiol HonFRCPA HonFACTM Senior Lecturer, University of Edinburgh; Emeritus Professor, Discipline of Pathology, Honorary Consultant Psychiatrist, Royal Brian W. Fleck, MD FRCOph University of Tasmania, Hobart, Tasmania, Hospital for Sick Children, Edinburgh, UK Consultant Ophthalmologist, Edinburgh Australia Royal Infirmary and Edinburgh Royal Richard F. Howard, BSc MBChB FRCA Hospital for Sick Children, Edinburgh, UK John R.W. Govan, BSc PhD DSc Consultant in Anaesthesia and Pain Professor of Microbial Pathogenicity, Management, Great Ormond Street Hospital Peter J. Fleming, PhD MB ChB FRCPCH FRCP Centre for Infectious Diseases, University of for Children, London, UK FRCP(C) Edinburgh Medical School, Edinburgh, UK Professor of Infant Health and Imelda Hughes, FRCPCH Developmental Physiology, University of Stephen M. Graham, FRACP Consultant Paediatric Neurologist, Bristol; Consultant Paediatrician, Royal Paediatric Research Fellow and Deputy Department of Paediatric Neurology, Hospital for Children, Bristol, UK Director Malawi-Liverpool-Wellcome Trust Royal Manchester Children’s Hospital, Clinical Research Programme, University Caroline Foster, MB BS MRCP of Malawi College of Medicine, Blantyre, Manchester, UK Honorary Clinical Research Fellow, Imperial Malawi; Senior Clinical Lecturer, Liverpool Robert Hume, BSc MB ChB PhD FRCPEdin FRCPCH College London; SPR Paediatric HIV, School of Tropical Medicine, Liverpool, UK Professor of Developmental Medicine, St Mary’s Hospital, London, UK Maternal and Child Health Sciences, Yvonne Freer, RGN RM RSCN BSc PhD Anne Green, BSc MSc PhD FRCPath FRCS FIBiol University of Dundee, Dundee, UK FRCPCH. Research and Practice Development Consultant Clinical Scientist, Birmingham Carol Inward, MBBCh MD FRCPCH Facilitator, Neonatal Intensive Care, Simpson Children’s Hospital NHS Trust, Consultant Paediatric Nephrologist, Bristol Centre for Reproductive Health, Royal Birmingham, UK Royal Hospital for Children, Bristol, UK Infirmary of Edinburgh, Edinburgh, UK Marcus Grompe, MD David Isaacs, MB BChir MD FRACP FRCPCH Vijeya Ganesan, MRCPCH, MD Director, Oregon Stem Cell Center; Professor, Senior Staff Specialist at Children’s Hospital Senior Lecturer in Paediatric Neurology, Department of Molecular and Medical at Westmead; Clinical Professor in Paediatric Institute of Child Health, University College Genetics, Oregon and Health Science University, Infectious Diseases, University of Sydney, London, London, UK Portland, Oregon, USA Sydney, Australia Anne S. Garden, FRCOG Henry L. Halliday, FRCPE FRCP FRCPCH Omar Ismayl, MD MSc MRCPCH Head of Department of Medicine and Chair of Child Health and Welfare Research Consultant Neurologist, Damascus University Director of the Centre for Medical Education, Group, Department of Child Health, Queen’s Children’s Hospital, Mezza, Damascus, Syria Lancaster University, Lancaster; Honorary University Belfast, Northern Ireland, UK Consultant in Paediatric and Adolescent Huw R. Jenkins, MA MD FRCP FRCPCH Gynaecology, Royal Liverpool Children’s Christina Halsey, BM BCh BA MRCP MRCPath Consultant Paediatric Gastroenterologist, Hospital, Liverpool; Honorary Consultant Leukaemia Research Fund Clinical Research Department of Child Health, University Gynaecologist, University Hospitals Fellow, Faculty of Medicine, Glasgow Hospital of Wales, Cardiff, Wales, UK Morecambe Bay Trust, Morecambe, UK University, Glasgow, UK Cheryl A. Jones, MB BS PhD FRACP Andrew R. Gennery, MD MRCP MRCPCH Cary O. Harding, MD Associate Professor, and Sub Dean DCH DipMedSci Assistant Professor, Molecular and Medical Postgraduate Studies, Discipline of Senior Lecturer and Honorary Consultant Genetics; Director of the Biochemical Paediatrics and Child Health, University of in Paediatric Immunology, BMT Institute of Genetics Clinical Laboratory, Oregon Health Sydney; Sydney, New South Wales, Australia Contributors xvii Christopher J.H. Kelnar, MA MD FRCP FRCPCH Alison Leaf, BSc MB ChB MD MRCP FRCPCH Ian McKinley, OBE BSc MB ChB DCH FRCP FRCPCH Professor of Paediatric Endocrinology, Consultant Neonatologist, Southmead Senior Lecturer in Child Health, McKay- Section of Child Life and Health, Division of Hospital, Bristol, UK Gordon Centre, Royal Manchester Children’s Reproductive and Developmental Sciences, Hospital, Manchester, UK Malcolm I. Levene, MD FRCPCH FMedSc University of Edinburgh, Edinburgh, UK Professor of Paediatrics and Child Health, Sheila A.M. McLean, LLB MLitt PhD LLD FRSE Alison M. Kemp, MB BCH DCH MRCP University of Leeds, Leeds General Infirmary, FRCGP FMedSci FRCP(Edin) FRSA FRCPCH FRCP(Edin) Leeds, UK International Bar Association Professor of Reader in Child Heath, Department of Child Law and Ethics in Medicine, University of Leesa M. Linck, MD MPH Health, Cardiff University, Cardiff, Wales Glasgow, UK Consultant Paediatrician, Alastair I.G. Kerr, MBChB FRCS(Edin & Glas) The Connty Clinic, Winthrop, Sabine Maguire, MB BCh BAO MRCPI FRCPI FRCPCH Consultant Otolaryngologist, Ear, Nose and Washington State, USA. Senior Lecturer in Child Health, Cardiff Throat Department, Royal Infirmary for Sick University, Department of Child Health, John H. Livingston, MB ChB FRCP FRCPCH Children, Edinburgh, UK Cardiff, UK Consultant Paediatric Neurologist, Alison M. Kesson, MB BS PhD FRACP FRCPA Department of Paediatric Neurology, Leeds Janice Main, FRCP(Edin) FRCP(Lond) Virologist, Microbiologist and Paediatric General Infirmary, Leeds, UK Reader and Consultant Physician in Infectious Disease Physician, The Children’s Infectious diseases and General Medicine, Stuart Logan, MB ChB MSc(Epidemiology) Hospital, Westmead, Sydney New South Department of Medicine, Imperial College, MSc(Econ) MRCP FRCPCH Wales; Conjoint Associate Professor, St Mary’s Hospital, London, UK Professor of Paediatric Epidemiology; Paediatrics and Child Health, University of Sydney, Sydney New South Wales, Australia Director, Institute of Health and Social Guy Makin, BA BM BCh PhD MRCP FRCPCH Care Research, Peninsula Medical School, Senior Lecturer in Paediatric Oncology, Maurice A. Kibel, FRCP(Edin) DCH(Lond). St Luke’s Campus, Exeter, UK University of Manchester; Honorary Emeritus Professor of Child Health, School Consultant Paediatric Oncologist, Diana N.J. Lockwood, BSc MD FRCP of Child and Adolescent Health,University of Royal Manchester Children’s Hospital, Consultant Physician and Leprologist, Cape Town, South Africa Manchester, UK Hospital for Tropical Diseases, London, UK Denise Kitchiner, MD FRCP FRCPCH Andrew J. Lyon, MA MB FRCP FRCPCH Timothy Martland, MB ChB MRCP MRCPCH Consultant Paediatric Cardiologist, Consultant Paediatric Neurologist, Consultant Neonatologist, Simpson Centre Royal Liverpool Children’s NHS Trust, Department of Paediatric Neurology, for Reproductive Health, Royal Infirmary of Liverpool, UK Royal Manchester Children’s Hospital, Edinburgh, Edinburgh, UK Manchester, UK Nigel J. Klein, BSc MB BS MRCP PhD FRCPCH Ronan Lyons, MD FFPH FFPHMI MPH DCH Professor of Infection and Immunity, Professor of Public Health, Centre for Health Amha Mekasha, MD MSc University College London; Head, Infectious Information, Research and Evaluation, Associate Professor of Paediatrics and Child Diseases and Microbiology Unit, Institute of School of Medicine, Swansea University, Health, Department of Paediatrics and Child Health; Head, Department of Infection, Swansea, UK Child Health, Addis Ababa University, University College London; Consultant in Adis Ababa, Ethiopia Infectious Diseases and Microbiology, Anita Macdonald, PhD BSc SRD Great Ormond Street Hospital NHS Trust, Consultant Dietician in Inherited Metabolic Craig Mellis, MB BS MPH MD FRACP London, UK Disorders, Birmingham Children’s Hospital, Head of School, Associate Dean, Central Birmingham, UK, Head of Dietetics, Clinic School, Faculty of Medicine, The David M. Koeller, MD Birmingham Children’s Hospital NHS Trust, University of Sydney, Sydney, Australia Associate Professor, Pediatrics and Molecular Birmingham, UK and Medical Genetics; Chief, Division Stefan Meyer, MD PhD MRCPCH of Metabolism, Department of Pediatrics, Mary McGraw, FRCP FRCPCH CRUK Clinician Scientist and Consultant Doernbecher Children’s Hospital, Oregon Consultant Paediatric Nephrologist, Paediatric Oncologist, Univeristy of Health and Science University, Portland, Bristol Royal Hospital for Children, Manchester, Royal Manchester Children’s Oregon, USA Bristol, UK Hospital and Young Oncology Unit, Christie Hospital, Manchester, UK, Stefan Meyer MD Sailesh Kotecha, MA FRCPCH PhD Keiran McHugh, FRCR FRCPI DCH PhD MRCPCH Consultant Paediatric Radiologist, Great Professor of Child Health, Department of Child Health, Wales College of Medicine, Ormond Street Hospital for Children, Alan E. Mills, MA MB DCP DPath FRCPA. Cardiff University, Cardiff, Wales, UK London, UK FFPathRCPI FACTM Consultant Pathologist, Dorevitch Pathology, Karen Kotloff, MD Neil McIntosh, DSc(Med) Bendigo, Victoria, Australia Professor of Child Life and Health, Professor, Pediatrics and Medicine, Center for Vaccine Development, University of Department of Child Life and Health, Elizabeth Molyneux, OBE FRCP FRCPCH FEM University of Edinburgh; Honorary Professor and Head of Department of Maryland School of Medicine, Baltimore, Consultant Paediatrician, Lothian University Paediatrics, College of Medicine, Blantyre, Maryland, USA Hospitals NHS Trust, Edinburgh, UK Malawi, C Africa. Ian A. Laing, MA MD FRCPE FRCPCH Consultant Neonatologist, Simpson Centre G.A. Mackinlay, MB BS LRCP FRCSEd Malcolm E. Molyneux, MD FRCP FMedSci FRCSEng FRCPCH Director, Malawi-Liverpool-Wellcome Trust for Reproductive Health, Royal Infirmary of Senior Lecturer, Department of Clinical Clinical Research Programme, College of Edinburgh, Edinburgh, UK Surgery, University of Edinburgh; Consultant Medicine, University of Malawi, Malawi; David G. Lalloo, MB BS MD FRCP Paediatric Surgeon, Department of Paediatric Professor of Tropical Medicine, School of Reader In Tropical Medicine, Liverpool Surgery, Royal Hospital for Sick Children, Tropical Medicine, University of Liverpool, School of Tropical Medicine, Liverpool, UK Edinburgh, UK Liverpool, UK xviii Contributors Kim Mulholland, MD FRACP Irene A.G. Roberts, MD FRCP FRCPath FRCPCH Children’s Hospital; Deputy Director,Oregon Professor of Child Health, London School DRCOG Clinical and Translational Research Institute, of Hygiene and Tropical Medicine, London, Professor of Paediatric Haematology and Oregon Health and Science University, UK, Infectious Disease Epidemiology Unit, Consultant Paediatric Haematologist, Portland, Oregon, USA London School of Hygiene and Tropical Hammersmith Hospital and St Mary’s Ben Stenson, MD FRCPCH FRCPE Medicine, London, UK Hospitals, Imperial College, London, UK Consultant Neonatologist, Simpson Centre Alan O. Mulvihill, FRCSI FRCSEd Peter T. Rudd, MD FRCPCH for Reproductive Health, Royal Infirmary of Consultant Ophthalmic Surgeon, Princess Consultant Paediatrician, Royal United Edinburgh, Edinburgh, UK Alexandra Eye Pavilion and Royal Hospital Hospital, Bath, UK Terence Stephenson, DM FRCP FRCPCH for Sick Children, Edinburgh, UK S.C. Robson, MD MRCOG Professor of Child Health; Dean, Richard W. Newton, MD FRCPCH FRCP Professor of Fetal Medicine, School of Faculty of Medicine and Health Consultant Paediatric Neurologist, Surgical and Reproductive Sciences, Newcastle Sciences, Medical School, University of Royal Manchester Children’s Hospital, University, Newcastle upon Tyne, UK Nottingham, Queen’s Medical Centre, Manchester, UK Nottingham, UK Jean-Baptiste Roullet, PhD Angus Nicoll, CBE FFPHM FRCP FRCPCH Associate Professor (Research), Division Stephen Stick, PhD MB BChir MRCP FRACP Director, Communicable Disease Surveilaance of Metabolism, Department of Paediatrics, Associate Professor, Department of Centre, Centre for Infection, Health Oregon Health and Science University, Respiratory Medicine, Princess Margaret Protection Agency, London, UK Portland, Oregon, USA; Adjunct Associate Hospital for Children, University of Western Professor of Pharmacology and Therapeutics, Australia, Australia James Y. Paton, MD, FRCPCH FRCPSG University of Calgary, Calgary, Alberta, Reader in Paediatric Respiratory Medicine, Stephen Sturgiss, MD MRCOG Canada Division of Developmental Medicine, Consultant in Obstetrics and Fetal Medicine, University of Glasgow, Royal Hospital for George Rylance, MB FRCPCH Royal Victoria Infirmary, Newcastle upon Sick Children, Glasgow, UK Consultant in Paediatrics, Department of Tyne, UK Child Health, Royal Victoria Infirmary, Michael A. Patton, MA MSc MBChB FRCPCH Newcastle upon Tyne, UK David Sweet, MD FRCPCH Professor of Medical Genetics and Consultant Consultant Neonatologist, Royal Maternity Medical Geneticist, Department of Medical Moin A. Saleem, MB BS FRCP PhD Hospital, Belfast, Northern Ireland, UK Genetics, St George’s Hospital Medical Reader and Honorary Consultant Paediatric Angela E. Thomas, MB BS PhD FRCPE FRCPath School, London, UK Nephrologist, Bristol Children’s Hospital, FRCPCH University of Bristol, Bristol, UK Consultant Paediatric Haematologist, Philip L. Pearl, MD Royal Hospital for Sick Children, Edinburgh, Associate Professor of Paediatrics and Alison Salt, MB BS MSc FRACP FRCPCH UK Neurology, Department of Neurology, Consultant Developmental Paediatrician, Children’s National Medical Center, Neurodisability Service, Great Ormond Street James Tooley, MB BS MRCPCH The George Washington University School Hospital for Children NHS Trust and Institute Consultant in Neonatal Medicine, Neonatal of Medicine, Washington DC, USA of Child Health, London, UK Intensive Care Unit, St Michael’s Hospital, Bristol, UK Gale A. Pearson, MB BS MRCP FRCPCH Jenefer Sargent, MA MB BCh MSc MRCPCH Consultant in Paediatric Intensive Consultant Developmental Paediatrician, E. Jane Tizard, MB BS, FRCP FRCPCH Care, Birmingham Children’s Hospital, Neurodisability Service, Great Ormond Consultant Paediatric Nephrologist, Bristol Birmingham, UK Hospital for Children NHS Trust, London, UK Royal Hospital for Children, Bristol, UK Stavros Petrou, BSc MPhil PhD Ayad Shafiq, FRCOphth MRCPPaeds DCH BM BCh Russell Viner, MB BS FRCPCH FRACP FRCP PhD MRC Senior Non-Clinical Research Fellow, Consultant Ophthalmologist, Royal Victoria Consultant in Adolescent Medicine and National Perinatal Epidemiology Unit, Hospital, Newcastle upon Tyne, UK Endocrinology, Department of Paediatrics, University of Oxford, Oxford, UK Middlesex Hospital, London, UK Jonathan R. Skinner, MB ChB FRCPCH FRACP MD Ian J. Ramage, FRCPCH Paediatric Cardiologist, Green Lane Paediatric Rachel Webster, BSc PhD DipRCPath Consultant Paediatric Nephrologist, Royal and Cardiac Services, Starship Children’s Clinical Scientist, Department of Clinical Hospital for Sick Children, Glasgow, UK Hospital, Auckland, New Zealand Biochemistry, Birmingham Children’s Hospital, Birmingham, UK John J. Reilly, BSc PhD Alan Smyth, MA MB BS MRCP MD FRCPCH Professor of Paediatric Energy Metabolism, Reader in Child Health, University of Philip D. Welsby, FRCP(Ed) University Division of Developmental Nottingham; Honorary Consultant in Consultant in Infectious Diseases, Infectious Medicine, Royal Hospital for Sick Children, Paediatric Respiratory Medicine, Disease Unit, Western General Hospital, Glasgow, UK Nottingham University Hospitals NHS Edinburgh, UK Trust, Nottingham, UK J.M. Rennie, MD FRCP FRCPCH DCH Johannes Wildhaber, MD PhD Consultant and Senior Lecturer in Neonatal Rosalind L. Smyth, MA MB BS MD FRCPCH Head, Division of Respiratory Medicine, Medicine, Elizabeth Garrett Anderson and Brough Professor of Paediatric Medicine, University Children’s Hospital, Zürich, Obstetric Hospital, University College London University of Liverpool, Liverpool, UK Switzerland Hospitals, London Robert D. Steiner, MD Anthony F. Williams, BSc DPhil MB BS Sam Richmond, MB BS FRCP FRCPCH Professor, Pediatrics and Molecular and FRCP FRCPCH Consultant Neonatologist, Sunderland Royal Medical Genetics; Vice Chair for Research, Reader in Child Nutrition, St George’s, Hospital, Sunderland, UK Department of Pediatrics, Doernbecher University of London, London, UK Contributors xix Bridget A. Wills, BmedSci BM BS MRCP DTM&H and Health, Department of Reproductive Christopher Wren, MB ChB FRCP FRCPCH Clinical Senior Lecturer in Paediatrics, and Developmental Sciences, University of Consultant Paediatric Cardiologist, Freeman University of Oxford – Wellcome Trust Edinburgh, Edinburgh, UK Hospital, Newcastle upon Tyne, UK Clinical Research Unit, Ho Chi Minh City, Rachael Wood, BSc MB ChB DCH MFH MFPH Vietnam Clinical Academic Fellow, Department David C. Wilson, MD FRCP FRCPCH of Public Health Sciences and Centre for Senior Lecturer in Paediatric International Public Health Policy University Gastroenterology and Nutrition, Child Life of Edinburgh, Edinburgh, UK